An M2-selective cholinergic ligand with suitable kinetics for receptor measurement would be desirable for studies of Alzheimer's disease. We have labeled a thiadiazol tetrahydropyridine [F18]fluoro-propyl-T1TP (FP-TZTP), previously demonstrated to be an M2-selective agonist (J Med Chem 38:5-8). PET studies were performed in isofluorane-anesthetized rhesus monkeys to determine the kinetic characteristics of this tracer. FP-TZTP (2-3 mCi) was administered and dynamic scans were acquired in 3D mode. The input function was determined from arterial blood samples with metabolite measurements by ThC. Time-activity curves from various brain regions were fitted to models with one or two tissue compartments. Tracer uptake in brain was very rapid as reflected in K1 values of 0.3 to 0.5 ml/min/ml in gray matter regions. The model with one tissue compartment was chosen to fit the ROI data, because adding a compartment often produced convergence failures, unrealistic parameter values, or increases in the uncertainty of the volume of distribution (V). V values, representing total tissue binding, were very similar in cortical regions, basal ganglia, and thalamus (23.5+/-6.0, 23.8+/-5.8, and 21.5+/-5.1 mVml, respectively) but significantly lower (p<.01) in cerebellum (13.1+/-2.4), consistent with the distribution of M2 cholinergic receptors. Displacement by cold parent compound reduced total binding by 30 to 44 percent. Pre- blocking with parent compound reduced total binding by 60 to 70 percent. Muscarinic antagonists did not affect FP-TZTP binding. A preliminary study with physostigmine, a cholinesterase inhibitor, showed 20 to 30 percent reduction in FP-TZTP uptake when administered by infusion beginning 30 min before the tracer. These studies were presented at the Society of Nuclear Medicine Annual Meeting in June 1996 (JNuclMed37:10P).